Effect of sustained endotoxemia on alpha1-adrenergic responsiveness in parenterally fed rats.
We investigated the effect of endotoxemia on alpha1-adrenergic receptor-mediated smooth muscle contraction as measured by mean arterial pressure (MAP) in response to incremental doses of a vasopressor. Twelve male Sprague-Dawley rats were randomized to receive parenteral nutrition alone (PN) or in combination with a continuous infusion of endotoxin (PN-LPS) for 48 hours. Incremental doses of phenylephrine were given and peak MAP response was recorded. The endotoxin group had a decreased rise in MAP with the same dose of phenylephrine compared with the control group (59 +/- 14 and 99 +/- 12 mm Hg, respectively, p<0.001). However, the baseline MAP was higher in the endotoxin group (102 +/- 18 and 71 +/- 7 mm Hg, respectively, p<0.002). The overall maximum effect was the same for both groups (161 +/- 16 and 170 +/- 8 mm Hg, respectively, p=NS). These data indicate that sustained endotoxemia does not result in desensitization of alpha1-adrenergic responsiveness. Other mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.
Dickerson
R N
RN
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163, USA.
Lima
J J
JJ
Kuhl
D A
DA
Brown
R O
RO
Hak
L J
LJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D019446:Endotoxemia / Q000503:physiopathology*; D004926:Escherichia coli; D008297:Male; D010288:Parenteral Nutrition; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine